| First Author | Murase R | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 13 | Pages | 6895-911 |
| PubMed ID | 26828067 | Mgi Jnum | J:232433 |
| Mgi Id | MGI:5779244 | Doi | 10.1074/jbc.M116.715672 |
| Citation | Murase R, et al. (2016) Group X Secreted Phospholipase A2 Releases omega3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility. J Biol Chem 291(13):6895-911 |
| abstractText | Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free omega3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized omega3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and omega3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2alpha) protects from colitis by mobilizing omega6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an omega3 PUFA mobilizerin vivo, segregated mobilization of omega3 and omega6 PUFA metabolites by sPLA2-X and cPLA2alpha, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization. |
